The drug has already been approved by the U.S. Food and Drug administration to treat adults with heart failure with reduced ejection fraction, where the heart muscle does not contract efficiently.
Results from the new placebo-controlled phase-3 trial, known as EMPEROR-Preserved, show that the drug is beneficial to the broader range of heart failure patients whose problem is that the ventricle doesn't fill with enough blood.
"The improvements were pretty substantial," coauthor Dr. Javed Butler, chairman of the department of medicine at the University of Mississippi Medical Center, in Jackson, told Reuters Health by phone.
"On the other hand, people wished there was a more robust mortality reduction than 9%," a non-significant finding, "so the search for mortality reduction continues," he said.
The research was presented during the European Society of Cardiology Congress 2021 and published online by the New England Journal of Medicine.
The results reflect "a major win against a medical condition that had previously proved formidable," Dr. Mark Drazner of the University of Texas Southwestern Medical Center, in Dallas, said in a linked editorial. The findings "should contribute to a change in clinical practice, given the paucity of therapeutic options available for patients with heart failure and a preserved ejection fraction."
The study was financed and conducted in part by Boehringer Ingelheim and Eli Lilly, which sell the drug under the brand name Jardiance.
Of the more than 6 million heart-failure cases in the United States accounting for more than a million hospital admissions each year, nearly half the patients have a preserved ejection fraction. Their treatment options are limited.
In the new study, nearly 6,000 volunteers at 622 centers in 23 countries were randomly assigned to receive empagliflozin or a placebo.
Patients were eligible if they had class II-IV heart failure and an ejection fraction of more than 40%. All received usual therapy. Nearly half were diabetic.
After a median of 26 months of therapy, 13.8% of the empagliflozin recipients and 17.1% of patients getting placebo were hospitalized for their heart failure or suffered a cardiovascular death, a 21% reduction in risk for the primary outcome (P<0.001).
The researchers calculated that 31 patients would need to be treated to prevent one primary-outcome event.
When the research team looked at hospitalization for heart failure alone, the rates were 8.6% and 11.8% respectively, a significant 29% reduction.
The difference in the odds of death from cardiovascular causes was not statistically significant. The rates of death from any cause were similar.
"The benefit accrues whether or not you have diabetes," Dr. Butler said.
The effect was most significant in patients with an ejection fraction below 50%, according to the primary outcome. When it was 60% or higher, the benefit was not statistically significant. Between those two values, the significance was borderline.
Empagliflozin recipients were a bit more likely to develop genital and urinary-tract infections, along with hypotension.
The companies said that's not surprising, reporting in a news release that, "the overall safety data was consistent with previous findings."
Empagliflozin, which is known to reduce the development and progression of heart failure in type-2 diabetics, is a sodium-glucose cotransporter 2 (SGLT2) inhibitor.
The treatment costs about $6,400 per year according to prices on the website goodrx.com.
The fact that the benefits are comparable in scope to what was seen in the EMPEROR-Reduced trial of patients with reduced ejection fraction "suggests that the effects of SGLT2 inhibition on heart failure events do not vary meaningfully with the heart failure phenotype," the researchers write.
Dr. Butler said one benefit of having a drug that works in patients with both reduced ejection fraction and preserved ejection fraction is that doctors can prescribe it immediately "while other tests are going on in the background" to determine the specific type of disease.
The journal also published an analysis of the drug's effects on serious renal outcomes and found that only patients with a reduced ejection fraction at the start of the trial saw a benefit.
The rate of serious renal outcomes was 49% lower among empagliflozin recipients enrolled in EMPEROR-Reduced but only 5% lower - a nonsignificant difference - among EMPEROR-Preserved patients.
SOURCE: https://bit.ly/3BoZwcT, https://bit.ly/3kGJ8xv and https://bit.ly/3gP0Rlh The New England Journal of Medicine, online August 27, 2021.
By Gene Emery
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